Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha, China.
Center for Medical Experiments, the Third Xiangya Hospital, Central South University, Changsha, China.
Immunol Invest. 2022 May;51(4):826-838. doi: 10.1080/08820139.2021.1877302. Epub 2021 Jan 27.
Kawasaki disease (KD)), also known as mucocutaneous lymph node syndrome (MCLS), is an autoimmune and systemic vasculitis syndrome. Its etiology and pathogenesis are still unclear. microRNAs (miRNA), a novel class of small non-coding RNAs, regulate the expression of multiple protein-encoding genes at the post-transcriptional level. We intend to study the change of miRNA-133a in the plasma of patients with KD, explore the role of miRNA-133a on HUVEC and define the pathogenesis of vascular dysfunction in KD. miRNA-133a expression and the mRNA and protein expression of protein phosphatase 2 catalytic subunit alpha (PPP2CA) were assessed by RT-qPCR and Western blot, respectively. The PPP2CA mRNA 3'UTR was predicted to be the potential target of miRNA-133a by using the miRNA databases and verified by the luciferase assay. The plasmids of miRNA-133a mimics and inhibitors were transfected into HUVEC cells. The plasma soluble vascular endothelial cadherin (sVE-cadherin, the excised extracellular part of VE-cadherin) levels were investigated by ELISA. The results suggested that miRNA-133a was increased by 3.8 times in the acute KD group and by 2.7 times in the convalescent KD group compared with the control group (both .000). is the target gene of miRNA-133a and its expression was inhibited by miRNA-133a acting on PPP2CA mRNA 3'UTR (.013). The plasma sVE-cadherin levels in the acute KD groups were increased compared with the control group (.024). The ROC curve analysis showed that the expression of miRNA-133a segregate acute KD patients from convalescent KD patients and healthy children. Our results suggest that miRNA-133a might be a new biomarker for KD.
川崎病(KD),又称黏膜皮肤淋巴结综合征(MCLS),是一种自身免疫性和系统性血管炎综合征。其病因和发病机制尚不清楚。微小 RNA(miRNA)是一类新型的小非编码 RNA,可在转录后水平调节多个蛋白编码基因的表达。我们旨在研究 KD 患者血浆中 miRNA-133a 的变化,探讨 miRNA-133a 对 HUVEC 的作用,并明确 KD 中血管功能障碍的发病机制。采用 RT-qPCR 和 Western blot 分别评估 miRNA-133a 的表达以及蛋白磷酸酶 2 催化亚基 α(PPP2CA)的 mRNA 和蛋白表达。利用 miRNA 数据库预测 PPP2CA mRNA 3'UTR 是 miRNA-133a 的潜在靶标,并通过荧光素酶测定进行验证。将 miRNA-133a 模拟物和抑制剂的质粒转染到 HUVEC 细胞中。通过 ELISA 检测血浆可溶性血管内皮钙黏蛋白(sVE-cadherin,VE-cadherin 的切除细胞外部分)水平。结果表明,与对照组相比,急性 KD 组 miRNA-133a 增加 3.8 倍,恢复期 KD 组增加 2.7 倍(均.000)。PPP2CA 是 miRNA-133a 的靶基因,miRNA-133a 通过作用于 PPP2CA mRNA 3'UTR 抑制其表达(.013)。与对照组相比,急性 KD 组血浆 sVE-cadherin 水平升高(.024)。ROC 曲线分析显示,miRNA-133a 的表达可将急性 KD 患者与恢复期 KD 患者和健康儿童区分开来。我们的研究结果表明,miRNA-133a 可能是 KD 的一个新的生物标志物。